pe
pep-05521 v1 CC-BY-SA-4.0

Nakoroxin antibacterial peptide

A small protein fragment that kills or slows the growth of bacteria; used only as a lab research tool.

statuscomputed targetANTIMICROBIAL length59 aa refs1
antibacterialantimicrobial
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 2 / 5 · 2 contributors
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.616
avg pLDDT70.9
ranking score0.690
STRUCTURE · PEP-05521 × ANTIMICROBIAL
ranking0.690
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RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence59 aa
151015202530354045505559
ECYRKSDIVTCEPWQKFCYR EVTFFPNHPVYLSGCASECT ETNSKWCCTTDKCNRARGG
in the news 6 articles
Hypotheses7 directions▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-05

If a molecule attacks tuberculosis, could it also fight the related lung bugs that kill cystic fibrosis patients?

Certain lung bacteria related to TB have become nearly impossible to treat, especially in cystic fibrosis patients. If this peptide targets the waxy outer shell these bacteria share with TB, it could open a door to treatments where almost none currently exist.

The hypothesis
Nakoroxin is active against non-tuberculous mycobacteria (NTM) including Mycobacterium avium complex and Mycobacterium abscessus, which share the lipid-rich cell envelope that the peptide likely targets, extending its utility to an increasingly prevalent and treatment-refractory infectious disease.
Why it’s plausible
The reference establishes activity against M. tuberculosis. NTM species share the defining mycobacterial cell-wall architecture (mycolic acids, arabinogalactan, lipoarabinomannan) that differentiates mycobacteria from other bacteria and likely determines susceptibility to Nakoroxin's mechanism. M. abscessus in particular is intrinsically resistant to most current antibiotics and lacks approved treatments. Repurposing a scaffold active against M. tuberculosis toward NTM is a small mechanistic step if the target is a conserved envelope component.
Why it matters
M. abscessus pulmonary infection in cystic fibrosis patients represents an unmet clinical need with essentially no curative therapy. Demonstrating NTM activity would immediately elevate Nakoroxin from a tuberculosis research tool to a candidate for a high-priority orphan indication.
Plausibility.55
Novelty.50
Impact.75
Basis · grounding2 papers · 1 computed/note
[1]
paper
Activity demonstrated against drug-resistant M. tuberculosis; the same cell-wall architecture present in NTM species is the likely molecular basis.
doi: 10.1016/s0924-8579(03)00110-9
[2]
sequenceCysteine-rich, disulfide-constrained scaffold resists serochresis by mycobacterial extracellular proteases, a shared defense across Mycobacterium genus members.
[3]
paper
Last-resort antibiotics for mycobacteria have narrow therapeutic indices; novel scaffolds with distinct mechanisms are urgently needed.
doi: 10.1038/s41467-020-16950-x
openupdated 2026-06-05

Does the peptide recognize and grip a unique sugar structure on TB's surface as its first step?

TB is coated in a complex sugar-fat shell that human cells do not have. If this peptide locks onto that structure first, it could explain why it kills TB while leaving human cells alone, and that targeting step could itself become a way to design better drugs.

The hypothesis
Nakoroxin binds directly to mycobacterial lipoarabinomannan (LAM) or a related surface-exposed glycolipid, and this carbohydrate-peptide interaction, mediated by the positively charged residues flanking the cysteine loops, is the primary recognition step preceding membrane disruption.
Why it’s plausible
The mycobacterial outer surface is dominated by LAM and related glycolipids that are absent from gram-positive and gram-negative bacteria but conserved across the Mycobacterium genus. Nakoroxin has multiple basic residues (R4, K5, K16, R20, K45, K52, R55, R57) distributed around the cysteine-constrained loops. In defensin-like peptides, cationic loops engage anionic surface glycolipids before membrane engagement. LAM is negatively charged and surface-exposed, making it a plausible electrostatic partner for this peptide.
Why it matters
If LAM is the primary recognition target, Nakoroxin's selectivity for mycobacteria over other bacteria would have a structural explanation grounded in the unique mycobacterial glycolipid coat, and this interaction would be a druggable node distinct from cell-wall biosynthesis inhibition.
Plausibility.47
Novelty.60
Impact.78
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceBasic residues R4, K5, K16, R20, K45, K52, R55, R57 are distributed across multiple loops constrained by the eight cysteines, creating a polyvalent cationic surface suited for engaging the anionic LAM headgroups.
[2]
paper
Activity specifically against Mycobacterium tuberculosis isolates from snake venom-derived peptides, pointing to a mycobacterium-specific structural feature as the recognition determinant.
doi: 10.1016/s0924-8579(03)00110-9
[3]
structureBoltz-2 computed structure; the spatial arrangement of basic residues on the peptide surface can be compared against the known LAM-binding sites of defensins.
openupdated 2026-06-05

Can a peptide kill bacteria without also damaging human cells, just because of the way it is shaped?

Many natural antibiotic peptides harm human red blood cells at roughly the same dose needed to kill bacteria, making them unsafe. If this peptide's rigid, clamp-like structure prevents it from punching through human cell membranes, it could have a much safer window for use in patients.

The hypothesis
Nakoroxin exhibits low mammalian cell toxicity relative to its antibacterial potency because its rigid cysteine-stabilized scaffold limits membrane insertion depth, preventing the extensive bilayer disruption that causes hemolysis in flexible alpha-helical AMPs.
Why it’s plausible
Many classical cationic AMPs cause hemolysis at concentrations near their MIC, limiting the therapeutic window. Cysteine-rich peptides with constrained scaffold geometry (defensins, tachyplesins) show superior selectivity indexes because the rigidity prevents the full peptide from adopting the deep transmembrane conformation required to lyse cholesterol-rich eukaryotic membranes. Nakoroxin's high cysteine content constrains backbone flexibility in exactly this way. The axis hit data shows selectivity was queried but no specific data exists for this peptide, making this non-trivially testable.
Why it matters
Selectivity is the principal early-stage hurdle for AMP therapeutics. Demonstrating that the scaffold geometry confers a favorable therapeutic index for Nakoroxin would validate a structural design principle for anti-TB peptide development.
Plausibility.50
Novelty.47
Impact.80
Basis · grounding2 papers · 1 computed/note
[1]
sequenceEight cysteines with four likely disulfide bonds produce a rigid backbone that cannot adopt the flexible amphipathic helix geometry required for deep eukaryotic membrane insertion.
[2]
paper
Selectivity of AMPs against bacteria versus mammalian cells is governed by physicochemical properties including secondary structure; rigid scaffolds behave differently from flexible helices.
doi: 10.3390/molecules26154654
[3]
paper
AMP selectivity can stem from membrane-composition targeting (bacteria vs. eukaryotes differ in lipid composition and surface charge) without requiring receptor-mediated specificity.
doi: 10.1128/aac.01341-13
openupdated 2026-06-05

Could a peptide from venom kill the TB strains that have beaten every antibiotic we have?

Drug-resistant TB kills hundreds of thousands of people a year and options are running out. If this peptide attacks TB's unique waxy outer shell in a way no current drug does, resistant strains would have no ready defense against it.

The hypothesis
Nakoroxin has bactericidal activity against drug-resistant Mycobacterium tuberculosis at clinically relevant concentrations and acts by disrupting the mycobacterial cell wall rather than the inner membrane, exploiting the unusual lipid-rich envelope of mycobacteria.
Why it’s plausible
The sole reference explicitly reports activity of venom-derived peptides against drug-resistant M. tuberculosis clinical isolates. Mycobacteria have a uniquely thick, waxy outer envelope (mycolic acids, arabinogalactan) that is impermeable to many membrane-active AMPs. A rigid cysteine-stabilized scaffold like Nakoroxin may penetrate this envelope through a different physical mechanism than alpha-helical AMPs, potentially by intercalating into the mycolic acid layer rather than forming transmembrane pores.
Why it matters
Drug-resistant tuberculosis remains a global health emergency. A venom-derived peptide with a novel scaffold and novel mechanism of action against drug-resistant M. tuberculosis would represent a fundamentally new class of anti-TB agent not subject to existing resistance mechanisms.
Plausibility.53
Novelty.35
Impact.88
Basis · grounding2 papers · 1 computed/note
[1]
paper
In vitro activities of small peptides from snake venom tested directly against clinical isolates of drug-resistant Mycobacterium tuberculosis.
doi: 10.1016/s0924-8579(03)00110-9
[2]
sequenceCysteine-rich rigid scaffold likely resists proteolytic degradation by mycobacterial enzymes, maintaining activity in the presence of bacterial proteases.
[3]
paper
SA and P. aeruginosa develop AMP resistance via proteolytic degradation; a disulfide-locked scaffold would resist this mechanism, relevant for chronic mycobacterial infection.
doi: 10.2147/ijn.s180040
openupdated 2026-06-05

Does having many internal bonds that lock a peptide's shape make it a better, more durable weapon against bacteria?

Most antibiotic peptides fall apart quickly in the bloodstream. If this peptide's eight internal locks give it a fortress-like shape that survives the body's digestive enzymes, it could stay active long enough to actually work as a medicine.

The hypothesis
Nakoroxin adopts a cysteine-stabilized alpha-beta (CS-alpha-beta) scaffold stabilized by four disulfide bonds formed from its eight cysteine residues, and this rigid scaffold rather than membrane charge alone is the structural basis of its antibacterial activity.
Why it’s plausible
The 59-mer sequence contains eight cysteines (positions 2, 11, 18, 35, 39, 47, 48, 53), an unusually high density for a peptide of this length. Four disulfide bonds would place this in the defensin or scorpion-toxin structural family, both of which use the CS-alpha-beta fold. Classical membrane-disrupting AMPs rarely contain more than two or four cysteines. The venom origin cited in the reference is consistent with a toxin-fold rather than a simple cationic helix.
Why it matters
If the scaffold rather than charge is primary, rational engineering must preserve the disulfide connectivity, and linearized or reduced forms would lose activity. This also predicts high proteolytic stability in serum, improving therapeutic outlook.
Plausibility.40
Novelty.60
Impact.80
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceEight cysteines in 59 residues (positions 2, 11, 18, 35, 39, 47, 48, 53) implies four potential disulfide bonds, consistent with defensin or toxin fold.
[2]
paper
Reference title identifies the peptide as derived from snake venom, a source known for cysteine-rich, disulfide-stabilized toxin scaffolds.
doi: 10.1016/s0924-8579(03)00110-9
[3]
structureBoltz-2 computed structure available; a CS-alpha-beta fold would manifest as a compact beta-sheet flanked by short helical segments stabilized by crossing disulfides.
openupdated 2026-06-05

Instead of tearing bacteria apart, could this peptide simply stop them from building their own walls?

Many antibiotic peptides kill by ripping open bacterial membranes, which can also hurt human cells. If this peptide instead grabs onto a small molecule bacteria need to build their walls, blocking it like a wrench in gears, it could be both more precise and less likely to cause side effects.

The hypothesis
Nakoroxin kills bacteria by binding to lipid II or another conserved cell-wall biosynthesis intermediate rather than by direct membrane permeabilization, a mechanism enabled by its rigid beta-sheet face that can contact the pyrophosphate-sugar headgroup of lipid II.
Why it’s plausible
Peptides with cysteine-rich, rigid beta-sheet scaffolds including defensins and some lantibiotics have been shown to sequester lipid II. Nakoroxin's MW (~6.8 kDa, 59 residues) and likely beta-sheet surface are within the range of lipid-II-binding defensins. The presence of aromatic residues (Y at positions 3, 19, 31; W at positions 14 and 46; F at positions 17, 24, 25) suggests a hydrophobic face capable of membrane insertion without gross permeabilization. Activity against the waxy mycobacterial envelope further points away from simple pore formation.
Why it matters
Lipid II is a conserved and essential target across gram-positive, gram-negative, and mycobacterial species. Confirming this mechanism would explain the broad-spectrum potential and inform a scaffold-based engineering strategy to enhance lipid-II affinity.
Plausibility.35
Novelty.65
Impact.77
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceAromatic residues W14, F17, Y19, F24, F25, W46 form a potential hydrophobic/aromatic face; eight cysteines constrain the backbone rigidity needed for lipid-II docking.
[2]
paper
Lipid-II sequestration by AMPs noted in the context of overcoming polymyxin-type resistance mechanisms.
doi: 10.1038/s41467-020-16950-x
[3]
structureBoltz-2 structure prediction; a compact structured fold with defined faces is consistent with a specific-target mechanism rather than non-specific membrane disruption.
openupdated 2026-06-05

Could scientists swap pieces of this peptide in and out, like building blocks, to tune it against specific resistant strains?

Discovering a new antibiotic scaffold from scratch takes years and large investments. If this peptide's frame stays stable while its surface loops can be swapped for pieces taken from other bacteria-killing molecules, researchers could mix and match to build a whole family of tailored drugs far faster.

The hypothesis
The cysteine-stabilized scaffold of Nakoroxin can serve as a rigid template into which active-site loop sequences from other defensins or antimycobacterial peptides can be grafted, producing chimeric variants with retained structural stability but altered target specificity.
Why it’s plausible
Scaffold grafting is well established for cystine-knot and CS-alpha-beta peptides: the disulfide framework maintains the three-dimensional shape while exposed loops can be replaced to install new recognition surfaces. Nakoroxin's 59-residue length, with cysteine-constrained loops, is a suitable scaffold. The loops between cysteines (e.g., the C2-C11 loop of 8 residues and the C18-C35 loop of 16 residues) are long enough to encode antimicrobial specificity determinants transplanted from other venom-derived or host-defense peptides.
Why it matters
If Nakoroxin's scaffold is modular, it opens a combinatorial design route to a family of anti-TB agents optimized for specific drug-resistant strains, bypassing the need to discover entirely new natural peptide scaffolds.
Plausibility.48
Novelty.40
Impact.60
Basis · grounding2 papers · 1 computed/note
[1]
sequenceLoop lengths between cysteine pairs: C2-C11 (8 residues), C11-C18 (6 residues), C18-C35 (16 residues), C35-C39 (3 residues), C39-C47 (7 residues), C47-C48 (1 residue), C48-C53 (4 residues); multiple loops are suitable for sequence substitution.
[2]
paper
Structural information is prerequisite for modifying natural peptides and predicting outcomes of changes for therapeutic optimization.
doi: 10.1016/j.jsb.2018.10.003
[3]
paper
Manufacturing costs for long peptides are a concern; scaffold-based design rather than de novo synthesis amortizes the cost by reusing a proven backbone.
doi: 10.1038/nbt1267
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.6902281641960144 boltz-2
3-letter notation
Glu-Cys-Tyr-Arg-Lys-Ser-Asp-Ile-Val-Thr-Cys-Glu-Pro-Trp-Gln-Lys-Phe-Cys-Tyr-Arg-Glu-Val-Thr-Phe-Phe-Pro-Asn-His-Pro-Val-Tyr-Leu-Ser-Gly-Cys-Ala-Ser-Glu-Cys-Thr-Glu-Thr-Asn-Ser-Lys-Trp-Cys-Cys-Thr-Thr-Asp-Lys-Cys-Asn-Arg-Ala-Arg-Gly-Gly
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategynone_monomer
runtime
predicted by
predicted at2026-05-23
citationbibtex
peptidemodel (2026). Nakoroxin antibacterial peptide (pep-05521, v1). PeptideModel. https://peptidemodel.com/card/pep-05521
@peptide{pep05521,
  sequence = {ECYRKSDIVTCEPWQKFCYREVTFFPNHPVYLSGCASECTETNSKWCCTTDKCNRARGG},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {computed}
}
references 1 papers
[1] source scaffold
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